Codeine (Oral)

KOE-deen

Oral route(Tablet)

Addiction, Abuse, and Misuse:Codeine sulfate exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing codeine sulfate, and monitor all patients regularly for the development of these behaviors or conditions.Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to: complete a REMS-compliant education program, counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products, emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety.Life-Threatening Respiratory Depression:Serious, life-threatening, or fatal respiratory depression may occur with use of codeine sulfate. Monitor for respiratory depression, especially during initiation of codeine sulfate or following a dose increase.Accidental Ingestion:Accidental ingestion of even one dose of codeine sulfate, especially by children, can result in a fatal overdose of codeine.Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children:Life-threatening respiratory depression and death have occurred in children who received codeine. Most of the reported cases occurred following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being an ultra-rapid metabolizer of codeine due to a CYP2D6 polymorphism. Codeine sulfate tablets are contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of codeine sulfate tablets in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeineNeonatal Opioid Withdrawal Syndrome:Prolonged use of codeine sulfate during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.Interactions with Drug Affecting Cytochrome P450 Isoenzymes:The effects of concomitant use or discontinuation of CYP3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. Use of CYP3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine sulfate requires careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine.Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants:Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of codeine sulfate and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation .

Uses For codeine

Codeine is used to relieve mild to moderate pain. It belongs to the group of medicines called narcotic analgesics (pain medicines). Codeine acts on the central nervous system (CNS) to relieve pain.

When codeine is used for a long time, it may become habit-forming, causing mental or physical dependence. However, people who have continuing pain should not let the fear of dependence keep them from using narcotics to relieve their pain. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be prevented by gradually reducing the dose over a period of time before treatment is stopped completely.

Codeine is available only under a restricted distribution program called the Opioid Analgesic REMS (Risk Evaluation and Mitigation Strategy) program.

Before Using codeine

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For codeine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to codeine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of codeine in the pediatric population. It should not be used in children younger than 12 years of age. Safety and efficacy have not been established.

Codeine sulfate tablets should not be used to relieve pain after surgery removal of tonsils or adenoids in any children 12 to 18 years of age. Severe breathing problems and deaths have been reported in some children who received codeine after tonsil or adenoid surgery.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of codeine in the elderly. However, elderly patients are more likely to have confusion and drowsiness, and age-related lung, liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving codeine in order to avoid potentially serious side effects.

Pregnancy

Pregnancy Category

Explanation

All Trimesters

C

Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using codeine.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking codeine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using codeine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

Furazolidone

Iproniazid

Isocarboxazid

Linezolid

Methylene Blue

Moclobemide

Nalmefene

Naltrexone

Nialamide

Phenelzine

Procarbazine

Rasagiline

Safinamide

Selegiline

Toloxatone

Tranylcypromine

Using codeine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Acepromazine

Alfentanil

Almotriptan

Alprazolam

Amineptine

Amiodarone

Amisulpride

Amitriptyline

Amitriptylinoxide

Amobarbital

Amoxapine

Amphetamine

Amprenavir

Anileridine

Aprepitant

Aripiprazole

Armodafinil

Asenapine

Atazanavir

Baclofen

Benperidol

Benzhydrocodone

Benzphetamine

Boceprevir

Bosentan

Bromazepam

Bromopride

Brompheniramine

Buprenorphine

Bupropion

Buspirone

Butabarbital

Butorphanol

Carbamazepine

Carbinoxamine

Carisoprodol

Carphenazine

Chloral Hydrate

Chlordiazepoxide

Chlorpheniramine

Chlorpromazine

Chlorzoxazone

Cimetidine

Cinacalcet

Ciprofloxacin

Citalopram

Clarithromycin

Clobazam

Clomipramine

Clonazepam

Clopidogrel

Clorazepate

Clozapine

Cobicistat

Cocaine

Conivaptan

Crizotinib

Cyclobenzaprine

Cyclosporine

Darunavir

Delavirdine

Desipramine

Desmopressin

Dexamethasone

Dexmedetomidine

Dextroamphetamine

Dextromethorphan

Dezocine

Diazepam

Dibenzepin

Dichloralphenazone

Difenoxin

Dihydrocodeine

Diltiazem

Diphenhydramine

Diphenoxylate

Dolasetron

Donepezil

Doxepin

Doxylamine

Dronedarone

Droperidol

Duloxetine

Efavirenz

Eletriptan

Enflurane

Enzalutamide

Erythromycin

Escitalopram

Eslicarbazepine Acetate

Estazolam

Eszopiclone

Ethchlorvynol

Ethopropazine

Ethylmorphine

Etravirine

Fentanyl

Flibanserin

Fluconazole

Fluoxetine

Fluphenazine

Flurazepam

Fluspirilene

Fluvoxamine

Fosamprenavir

Fosaprepitant

Fosnetupitant

Fosphenytoin

Fospropofol

Frovatriptan

Granisetron

Haloperidol

Halothane

Hexobarbital

Hydrocodone

Hydromorphone

Hydroxytryptophan

Hydroxyzine

Idelalisib

Imatinib

Imipramine

Indinavir

Isoflurane

Itraconazole

Ivacaftor

Ketamine

Ketazolam

Ketobemidone

Ketoconazole

Levomilnacipran

Levorphanol

Lisdexamfetamine

Lithium

Lofepramine

Lofexidine

Lomitapide

Lopinavir

Lorazepam

Lorcaserin

Loxapine

Lumacaftor

Meclizine

Melitracen

Melperone

Meperidine

Mephobarbital

Meprobamate

Meptazinol

Mesoridazine

Metaxalone

Methadone

Methamphetamine

Methdilazine

Methocarbamol

Methohexital

Methotrimeprazine

Metoclopramide

Mibefradil

Midazolam

Mifepristone

Milnacipran

Mirabegron

Mirtazapine

Mitotane

Modafinil

Molindone

Moricizine

Morphine

Morphine Sulfate Liposome

Nafcillin

Nalbuphine

Naratriptan

Nefazodone

Nelfinavir

Netupitant

Nevirapine

Nicomorphine

Nilotinib

Nitrazepam

Nitrous Oxide

Nortriptyline

Olanzapine

Ondansetron

Opipramol

Opium

Opium Alkaloids

Orphenadrine

Oxazepam

Oxcarbazepine

Oxycodone

Oxymorphone

Palbociclib

Palonosetron

Papaveretum

Paregoric

Paroxetine

Pentazocine

Pentobarbital

Perampanel

Perazine

Periciazine

Perphenazine

Phenobarbital

Phenytoin

Piperacetazine

Pipotiazine

Piritramide

Posaconazole

Prazepam

Prednisone

Primidone

Prochlorperazine

Promazine

Promethazine

Propofol

Protriptyline

Quazepam

Quetiapine

Quinidine

Quinine

Ramelteon

Ranitidine

Ranolazine

Remifentanil

Remoxipride

Rifabutin

Rifampin

Rifapentine

Ritonavir

Rizatriptan

Rolapitant

Saquinavir

Secobarbital

Sertindole

Sertraline

Sibutramine

Sodium Oxybate

St John's Wort

Sufentanil

Sulpiride

Sumatriptan

Suvorexant

Tapentadol

Telaprevir

Telithromycin

Temazepam

Terbinafine

Thiethylperazine

Thiopental

Thiopropazate

Thioridazine

Tianeptine

Tilidine

Tizanidine

Tolonium Chloride

Topiramate

Tramadol

Trazodone

Triazolam

Trifluoperazine

Trifluperidol

Triflupromazine

Trimeprazine

Trimipramine

Tryptophan

Venlafaxine

Verapamil

Vilazodone

Voriconazole

Vortioxetine

Zaleplon

Ziprasidone

Zolmitriptan

Zolpidem

Zopiclone

Zotepine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using codeine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use codeine, or give you special instructions about the use of food, alcohol, or tobacco.

Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of codeine. Make sure you tell your doctor if you have any other medical problems, especially:

Drug dependence, especially narcotic abuse or dependence, or history of or

Enlarged prostate (BPH, prostatic hypertrophy) or

Head injuries or

Hypothyroidism (an underactive thyroid) or

Kyphoscoliosis (curvature of spine that can cause breathing problems) or

Mental health problems, history of or

Obesity (overweight) or

Problems with passing urine or

Stomach or digestion problems—Use with caution. May increase risk for more serious side effects.

Breathing problems (eg, asthma, hypercapnia), severe or

Respiratory depression (hypoventilation or slow breathing) or

Stomach or bowel blockage (including paralytic ileus)—Should not be used in patients with these conditions.

Hypotension (low blood pressure) or

Pancreatitis (swelling of the pancreas) or

Seizures, history of—Use with caution. May make these conditions worse.

Kidney disease or

Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Proper Use of codeine

Take codeine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. This is especially important for elderly patients, who may be more sensitive to the effects of pain medicines. If too much of codeine is taken for a long time, it may become habit-forming (causing mental or physical dependence) or cause an overdose.

It is very important that you understand the rules of the Opioid Analgesic REMS program to prevent addiction, abuse, and misuse of codeine. Codeine should also come with a Medication Guide. Read and follow these instructions carefully. Read it again each time you refill your prescription in case there is new information. Ask your doctor if you have any questions.

Codeine is taken only when needed, so there are no special instructions for a missed dose.

Dosing

The dose of codeine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of codeine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage form (tablets):

For mild to moderate pain:

Adults—At first, 15 to 60 milligrams (mg) every 4 hours as needed. Your doctor may increase your dose as needed. However, the dose is usually not more than 360 mg per day.

Children 12 to 18 years of age—Use and dose must be determined by your doctor.

Children younger than 12 years of age—Should not be used in these patients.

Missed Dose

If you miss a dose of codeine, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Codeine can cause serious unwanted effects if taken by adults, children, or pets who are not use to strong narcotic pain medicines. Make sure you store the medicine in a safe and secure place to prevent others from getting it.

Precautions While Using codeine

It is very important that your doctor check your progress while you are using codeine, especially within the first 24 to 72 hours of treatment. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to use it. Blood tests may be needed to check for unwanted effects.

Do not use codeine if you are using or have used an MAO inhibitor (MAOI) such as isocarboxazid [Marplan®], linezolid [Zyvox®], phenelzine [Nardil®], selegiline [Eldepryl®], tranylcypromine [Parnate®]) within the past 14 days.

Check with your doctor before using codeine with alcohol or other medicines that affect the central nervous system (CNS). The use of alcohol or other medicines that affect the CNS with codeine may worsen the side effects of codeine, such as dizziness, poor concentration, drowsiness, unusual dreams, and trouble with sleeping. Some examples of CNS depressants are antihistamines or medicine for hay fever, allergies, or colds, sedatives, tranquilizers, or sleeping medicines, medicine for depression, medicine for anxiety, prescription pain medicine or narcotics, medicine for attention deficit and hyperactivity disorder, medicine for seizures or barbiturates, muscle relaxants, or anesthetics (numbing medicines), including some dental anesthetics. This effect may last for a few days after you stop taking codeine.

Codeine may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose. Call your doctor for instructions.

Dizziness, lightheadedness, or fainting may occur when you get up suddenly from a lying or sitting position. Getting up slowly may help. Also, lying down for a while may relieve dizziness or lightheadedness. If this problem continues or gets worse, check with your doctor right away.

Codeine may make you dizzy, drowsy, confused, or disoriented. Do not drive or do anything else that could be dangerous until you know how codeine affects you.

Using narcotics for a long time can cause severe constipation. To prevent this, your doctor may direct you to take laxatives, drink a lot of fluids, or increase the amount of fiber in your diet. Be sure to follow the directions carefully, because continuing constipation can lead to more serious problems.

Do not change your dose or suddenly stop using codeine without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This may help prevent worsening of your condition and reduce the possibility of withdrawal symptoms, such as abdominal or stomach cramps, anxiety, fever, nausea, runny nose, sweating, tremors, or trouble with sleeping.

Using codeine while you are pregnant may cause serious unwanted effects, including neonatal withdrawal syndrome in your newborn baby. Tell your doctor right away if you think you are pregnant or if you plan to become pregnant while using codeine.

Codeine is changed to morphine in the body. Some people change codeine to morphine more quickly than others. These individuals are called "ultra-rapid metabolizers of codeine". Contact your doctor immediately if you experience extreme sleepiness, confusion, or shallow breathing. These symptoms may indicate that you are an "ultra-rapid metabolizer of codeine". As a result, there is too much morphine in the body and more side effects of morphine than usual. Children may be especially sensitive to this effect. Do not give codeine to:

Children younger than 12 years of age.

Children younger than 18 years of age who have had surgery removal of tonsils or adenoids.

Children 12 to 18 years of age who have a high risk for breathing problems (eg, obstructive sleep apnea, obesity, lung disease).

If a nursing mother is an ultra-rapid metabolizer of codeine, it could lead to a morphine overdose in the nursing baby and cause very serious side effects.

For nursing mothers taking codeine:

Talk to your doctor if you have any questions about taking codeine or about how codeine may affect your baby.

Call your doctor if you become extremely tired and have difficulty caring for your baby.

Your baby should generally nurse every 2 to 3 hours and should not sleep more than 4 hours at a time.

Check with your doctor right away if you have anxiety, restlessness, a fast heartbeat, fever, sweating, muscle spasms, twitching, nausea, vomiting, diarrhea, or see or hear things that are not there. These may be symptoms of a serious condition called serotonin syndrome. Your risk may be higher if you also take certain other medicines that affect serotonin levels in your body.

Using too much of codeine may cause reduced infertility (unable to have children). Talk with your doctor before using codeine if you plan to have children.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Codeine Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Incidence not known

Bloating

blurred vision

chills

cold, clammy skin

confusion

constipation

darkened urine

difficult or troubled breathing

dizziness

dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position

fainting

fast, irregular, pounding, or racing heartbeat or pulse

fast, weak pulse

feeling of warmth

fever

indigestion

irregular, fast or slow, or shallow breathing

lightheadedness

loss of appetite

nausea

no blood pressure or pulse

no breathing

pains in the stomach, side, or abdomen, possibly radiating to the back

pale or blue lips, fingernails, or skin

redness of the face, neck, arms, and occasionally, upper chest

stopping of the heart

sweating

unconsciousness

unusual tiredness or weakness

vomiting

yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

Bluish lips or skin

chest pain or discomfort

constricted, pinpoint, or small pupils (black part of the eye)

decreased awareness or responsiveness

extreme sleepiness or unusual drowsiness

slow or irregular heartbeat

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Drowsiness

relaxed and calm feeling

Incidence not known

Diarrhea

disturbed color perception

double vision

dry mouth

false or unusual sense of well-being

fear or nervousness

feeling of constant movement of self or surroundings

halos around lights

headache

hives or welts, itching, or skin rash

night blindness

overbright appearance of lights

redness of the skin

sensation of spinning

shakiness

stomach pain or cramps

trouble sleeping

tunnel vision

weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.